Platelet Cofactors as Plasma Components of the Intrinsic Blood Clotting Mechanisms^[*]

Summary

The method for the assay for platelet cofactors has been overhauled to make allowance for an adequate and uniform supply of Ac-globulin. Thrombin is added at zero time to reduce variability of response in the activation of prothrombin. The potency of purified platelet cofactor I is about twice that of platelet cofactor II (autoprothrombin II). The total mass of platelet factor 3 plus platelet cofactor I or platelet cofactor II is much greater in the conversion of a given amount of purified prothrombin to thrombin than when brain thromboplastin is used.

In plasma and serum from the human being barium carbonate adsorbs platelet cofactor II, and ether extraction frees activity that is not adsorbed on barium carbonate before ether extraction. The extract contains an inhibitor(s) of prothrombin activation. The inhibition is strong in the intrinsic as well as the extrinsic prothrombin activation mechanisms. In the case of bovine plasma barium carbonate adsorption leaves the plasma richer in platelet cofactor activity and in that respect it differs from the plasma from human beings. Dog plasma and serum is comparable to that from man than the bovine species.

The lipids extracted from plasma or serum with ether are predominantly anticoagulant. Since platelet cofactor I activity disappears during the clotting of blood, we think that a function of platelet cofactor I is to be the receptor for an anticoagulant. Then as autoprothrombin II arises from prothrombin it serves as a procoagulant and is not retarded by the anticoagulant neutralized by platelet cofactor I.

• References

• 1 Seegers W. H, Mammen E, Lee J. M, Landaburu R. H, Cho M. H, Baker W. J, Shepard R. S. Further studies on the purification of platelet cofactor I. In Brinkhous K. M. (Edit.) Hemophilia and other Hemorrhagic States. The University of North Carolina Press; 38 Chapel Hill: 1959
• 2 Shulman S, Landaburu R. H, Seegers W. H. Biophysical studies on platelet cofactor I preparations. Thromb. Diath. haem. in press, 1960
• 3 Baker W. J, Seegers W. H. Some properties of platelet cofactor I concentrates of bovine origin. Thromb. Diath. haem. in press, 1960
• 4 Graham J. P, Penick G. D, Brinkhous K. M. Utilization of antihemophilic factor during clotting of canine blood and plasma. Amer. J. Physiol. 164: 170 1951;
• 5 Johnson S. A, Seegers W. H. Studies on the plasma defect in hemophilia. Rev. Hémat. 09: 529 1954;
• 6 Mammen E. F, Thomas W. R, Seegers W. H. Activation of purified prothrombin to autoprothrombin I or autoprothrombin II (platelet cofactor II) or autoprothrombin II-A. Thromb. Diath. haem. in press, 1960
• 7 Seegers W. H. The purification of prothrombin. Rec. Chem. Progress 13: 143 1952;
• 8 Ware A. G, Seegers W. H. Two-stage procedure for the quantitative determination of prothrombin concentration. Amer. J. clin. Path 19: 471 1949;
• 9 Seegers W. H, Smith H. P. Factors which influence the activity of purified thrombin. Amer. J. Physiol. 137: 348 1942;
• 10 Seegers W. H, Levine W. G, Shepard R. S. Further studies on the purification of thrombin. Canad. J. Biochem. Physiol. 36: 603 1958;
• 11 Johnson S. A, Seegers W. H. Use of purified prothrombin in the study of hemophilia and plasma thromboplastin component (PTC) deficiency. J. appl. Physiol. 06: 429 1954;
• 12 Alkjaersig N, Abe T, Seegers W. H. Purification and quantitative determination of platelet factor 3. Amer. J. Physiol. 181: 304 1955;
• 13 Murphy R. C, Ware A. G, Seegers W. H. Plasma Ac-globulin activity. Amer. J. Physiol. 151: 338 1947;
• 14 Hecht E, Cho M. H, Seegers W. H. Thromboplastin: Nomenclature and preparation of protein-free material different from platelet factor 3 or lipid activator. Amer. J. Physiol. 193: 584 1958;
• 15 Johnson S. A, Rutzky J, Schneider C. L, Seegers W. H. Activation of purified prothrombin with hemophilia plasma. Proc. 4th Internat. Congr. Internat. Soc. Hemat., Buenos Aires. 1952
• 16 Seegers W. H. A theoretical consideration of the blood clotting mechanisms in hemophilia. Schweiz, med. Wschr. 29: 781 1954;
• 17 Johnson S. A, Deutsch E, Seegers W. H. Ultracentrifugal separation of coagulation factors: Platelet cofactors and inhibitors. Amer. J. Physiol. 179: 149 1954;
• 18 Johnson S. A, McClaughry R. I, Seegers W. H. Nature of the blood clotting mechanisms in hemophilia. J. Mich. State Med. Soc. 54: 797 1955;
• 19 Johnson S. A. Activation of purified prothrombin with hemophilic plasma Amer J. clin. Path. 23: 875 1953;
• 20 Hecht E, Landaburu R. H, Seegers W. H. Spingosine as inhibitor of prothrombin activation with thromboplastin or with threone. Amer. J. Physiol. 189: 203 1957;
• 21 Hecht E, Landaburu R. H, Cho M. H, Seegers W. H. Die Angriffspunkte des Sphingosins, eines physiologischen Hemmstoffes der Blutgerinnung. Hoppe- Seyler’s 2. physiol. Chemie. 307: 263 1957;
• 22 Penner J. A, Seegers W. H. Activation of prothrombin. Amer. T Phvsiol. 186: 343 1956;
• 23 Graham J. B, Barrow E. M. The pathogenesis of hemophilia, an experimental analysis of the anticephalin hypothesis in hemophilic dogs. J. exper. Med. 106: 273 1957;
• 24 Mustard J. F. The serum defect in Christmas disease. Acta haemat. 21: 321 1959;
• 25 Brinkhous K. M. A study of the clotting defect in hemophilia: The delayed formation of thrombin. Amer. J. med. Sci. 198: 509 1939;
• 26 Johnson J. F, Mammen E. F, Seegers W. H. Prothrombin utilization following addition of platelet cofactor I concentrates to hemophilic plasma. Thromb. Diath. haem. 03: 588 1959;